# Adenosine‐to‐inosine editing of miR‐200b‐3p is associated with the progression of high‐grade serous ovarian cancer

## TL;DR

A specific type of RNA editing in miR-200b-3p is linked to worse outcomes in ovarian cancer and may offer new treatment strategies.

## Contribution

The study reveals that A-to-I editing of miR-200b-3p promotes high-grade serous ovarian cancer progression.

## Key findings

- Edited miR-200b-3p increases cancer cell proliferation, migration, and 3D spheroid formation.
- Higher editing levels of miR-200b-3p correlate with significantly worse patient survival.
- Edited miR-200b-3p inhibits cell-cycle pathways and targets tumor suppressor MXI1.

## Abstract

Deamination of adenosine to inosine (A‐to‐I) in double‐stranded microRNAs (miRNAs) has been demonstrated to affect their function as suppressors or oncogenes in various cancers. Nevertheless, the functional impact of miRNA editing in high‐grade serous ovarian cancer (HGSOC) remains largely unexplored. Here, we identified A‐to‐I editing in miRNAs in 60 HGSOC tissues and 48 ovarian tissues received in nononcological procedures using small RNA sequencing (RNA‐Seq). To investigate the functional impact of A‐to‐I modifications, we tested the effect of edited RNA mimics and small interfering RNA (siRNA)‐mediated downregulation of the RNA‐editing enzyme double‐stranded RNA‐specific editase Adar (ADAR1) on cell proliferation, migration and three‐dimensional (3D) growth of HGSOC cells in vitro. Tumour suppressor miR‐200b‐3p was the most overedited miRNA in HGSOC tumours, and the increased editing level was associated with statistically significant worse overall survival (OS). Mechanistically, in contrast to wild‐type miRNA, edited miR‐200b‐3p promoted cell proliferation, migration and formation of 3D spheroids. Loss of function of ADAR1 profoundly repressed proliferation, migration and 3D growth of HGSOC cells. RNA‐Seq and Gene Set Enrichment Analysis (GSEA) analysis revealed that, whereas wild‐type miR‐200b‐3p induced the apoptosis pathway, edited miR‐200b‐3p substantially inhibited cell‐cycle‐related pathways. Bioinformatic prediction revealed that edited miR‐200b‐3p gained the function to repress the expression of new targets, including tumour suppressor MAX interactor 1, dimerisation protein (MXI1), which was associated with a statistically significantly worse OS time in HGSOC patients. Our study reports the potential contribution of edited miR‐200b‐3p in HGSOC progression, and highlights its potential as a new therapeutic target.

A‐to‐I editing of miRNAs, particularly miR‐200b‐3p, contributes to HGSOC progression by enhancing cancer cell proliferation, migration and 3D growth. The edited form is linked to poorer patient survival and the identification of novel molecular targets. These findings highlight its potential as a biomarker and therapeutic target in ovarian cancer.